Bone disease in pediatric chronic kidney disease

Abstract

Children with long-standing chronic kidney disease (CKD) display clinical symptoms of bone disease, including bony deformities and fractures, which contribute to long-standing disability. Abnormalities in skeletal mineralization occur in a substantial proportion of this population and may contribute to chronic morbidity. Underscoring the potential contribution of parameters other than bone turnover to bone disease in CKD, a new definition for renal osteodystrophy (ROD), emphasizing the assessment of three key histologic descriptors, i.e., bone turnover (T), mineralization (M), and volume (V) (TMV), has been recommended in the assessment of all patients with CKD. Although bone biopsy is the only available method for assessing all three recommended areas of bone histology, this invasive procedure is not routinely used in any clinical setting; thus, a true understanding of the prevalence of abnormal turnover, defective mineralization, and altered bone volume throughout the course of CKD is limited. Recent data, however, have shed light on the progression of renal ROD throughout the course of CKD, including its early stages, as well as on the alterations in cell biology that accompany ROD.

Fig. 1

Serum values of phosphate (a), parathyroid hormone (PTH) (b), and fibroblast growth factor 23 (FGF23) (c) in a cross-section of pediatric patients with pre-dialysis chronic kidney disease (CKD). *P< 0.01 CKD stage 1–2 vs. CKD stage 3, ***P<0.001 CKD stage 1–2 vs. CKD stage 4, ***P<0.001 CKD stage 1–2 vs. CKD stage 5. Boxes and bars Interquartile range and median value, respectively, whiskers distance to the smallest and largest unbooked sample value. Reprinted with permission (van Husen et al. Kidney Int 2010; 78:200–206 [19])

Fig. 2

Prevalence of increased rates of bone formation rate (black bar), mineralization defect (white bar), increased parathyroid hormone (PTH) levels (striped bar), and increased FGF 23 values (black polka-dotted bar) in pediatric patients with Chronic Kidney disease (CKD). The mineralization defect was defined as an abnormal accumulation of osteoid (osteoid volume) in combination with a delay osteoid maturation time. Increased PTH values were defined as values above the range currently recommended by the Kidney Disease Outcomes Quality Initiative for CKD in children. Increased FGF23 values were defined as values above the range determined in healthy children. Reprinted with permission (Wesseling-Perry et al. Clin J Am Soc Nephrol. 2012; 7:146–52 [21])

Fig. 3

Fibroblast growth factor 23 (FGF23) expression (arrows) is markedly increased in patients with early (stage 2) Chronic Kidney disease (CKD) (b) as compared to control (a). BM Bone marrow, TB trabecular bone. Arrows indicate osteocytes with positive staining for FGF 23. Reprinted with permission (Pereira RC et al. Bone 2009; 45:1161–1168 [40])

Fig. 4

Dentin matrix protein 1 (DMP1) expression is markedly increased in patients with early (stage 2) CKD (b) as compared to control (a). Arrows indicate osteocytes with positive staining for DMP1. Reprinted with permission (Pereira RC et al. Bone 2009; 45:1161–1168 [40])